Neuroendocrine control of pulsatile GnRH secretion during the ovarian cycle: evidence from the ewe

Abstract

This article reviews the neuroendocrine control of episodic GnRH secretion during the ovine oestrous cycle. There is general agreement that endogenous opioid peptides (EOPs) mediate the negative feedback action of progesterone on GnRH pulse frequency during the luteal phase of the ovarian cycle and recent preliminary data have implicated the dynorphin-kappa-receptor system in this effect of progesterone. Progesterone also acutely inhibits GnRH pulse frequency via a non-EOP mechanism, as naloxone does not block the rapid effects of this steroid. The effects of bicuculline, 3alpha-hydroxy-5alpha-pregnan-20-one and RU486 consistently indicated that the gamma-aminobutyric acid A (GABA-A) receptor is also not involved in the acute actions of progesterone. Thus, the neural system mediating this effect remains to be determined. Oestradiol has several actions on episodic GnRH secretion. The most well characterized action is inhibition of GnRH pulse amplitude, which is probably mediated by noradrenergic neurones. Oestradiol also increases the response to progesterone negative feedback, alters GnRH pulse shape and increases GnRH pulse frequency. The first two of these actions may involve EOPs, whereas the mechanisms underlying GnRH pulse frequency are currently unknown. Finally, there is also evidence that EOPs play a physiological role in synchronizing the firing of the GnRH neurones responsible for episodic release. Specifically, the effects of naloxone on the GnRH pulse shape lead to the hypothesis that EOP tone contributes to the termination of each GnRH pulse and prevents random firing of these GnRH neurones between pulses. Thus, it appears that EOPs play an important role in controlling several different aspects of pulsatile GnRH release during the ovine oestrous cycle.